Idiopathic inflammatory myopathy (poly-dermatomyositis) is an inflammatory disease of muscle in which characteristic autoantibodies occur. By applying a broad range of immunological, clinical, and epidemiological observations to a large (expanded in the past year to over 250) group of patients, we have developed evidence for subsets of patients which strongly suggest that the disease can be divided into more meaningful groups with different etiology, pathogenesis and response to therapy. Studies on the seasonal and geographic distribution of disease sub-types are well underway. Laboratory studies have shown that the major autoantibody, anti-Jo-1, which defines a clinically important subgroup of patients, appears to be an antigen-driven secondary response directed to a conformational, not a linear, epitope of histidyl tRNA synthetase. The discovery of affinity-maturation in the early response to this antigen powerfully implicates the enzyme itself as the driving antigen.